hK2 and free PSA, a prognostic combination in predicting minimal prostate cancer in screen-detected men within the PSA range 4-10 ng/ml.

OBJECTIVES: The purpose of screening for prostate cancer is to decrease the disease-specific mortality. However not every screen-detected prostate cancer is a threat to the patient's life. The risk of overdetection and subsequent overtreatment in prostate cancer has been recognised. The purpose of this investigation was to evaluate the role of tumour markers total PSA, free PSA, and hK2, and their combinations in predicting minimal prostate cancer. METHODS: Within the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, The Netherlands, prebiopsy serum samples were analysed for 100 selected men who underwent a radical prostatectomy for their screen-detected prostate cancer. All had a PSA value between 4 and 10 ng/ml prior to diagnosis. Minimal prostate cancer is defined as organ confined, Gleason score

Overall and disease-specific survival of patients with screen-detected prostate cancer in the European randomized study of screening for prostate cancer, section Rotterdam.

INTRODUCTION: This report describes survival data of participants of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, diagnosed with prostate cancer (pCA) during the first round of screening, the prevalence screen. PATIENTS AND METHODS: pCA characteristics from cases diagnosed during the first screening round from December 1993 to March 2000 are shown. During follow-up, data were collected by semiannual patient chart review for the first 5 yr and annually thereafter. The causes of death are scored according to the diagnosis of the treating physician and are not based on the review of the independent causes-of-death committee. Overall and disease-specific survival graphs are shown in Kaplan-Maier projections and compared with expected survival outcomes for males in the same age categories from the Dutch provinces of North Holland and Flevoland. Statistical evaluation was based on Cox regression analysis. RESULTS: During the prevalence screening, 1014 patients were diagnosed with pCA. Median follow up was 55 mo, 126 (12.4%) patients died, 20 (2.0%) of pCA. Overall 5-yr observed and expected disease-specific survival was 97.7% and 82%, respectively. In the multivariate analysis, a Gleason sum of 4+4 or higher (p=0.025) was predictive of pCA death. CONCLUSIONS: The observed survival data are in line with the literature and the expected favorable outcome for a screened population. The proportion of men dying from pCA is still small, and a 10-yr follow-up period for the final evaluation of the ERSPC may be too short.

Active surveillance for prostate cancers detected in three subsequent rounds of a screening trial: characteristics, PSA doubling times, and outcome.

OBJECTIVES: To study active surveillance as a management option for the important number of prostate cancer patients who would not have been diagnosed in the absence of screening. PATIENTS AND METHODS: We analyzed baseline characteristics and outcome parameters of all men on active surveillance who were screen-detected in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Recruitment and surveillance of men were not guided by a protocol but depended on individual decisions of patients and their physicians. RESULTS: Active surveillance was applied in 278 men detected by screening from 1993 to 2006. At diagnosis, their median age was 69.8 yr (25-75p; 66.1-72.8); median PSA 3.6 ng/ml (25-75p; 3.1-4.8), and the clinical stage was T1c in 220 (79.1%) and T2 in 58 (20.9%). During the follow-up of median 3.4 yr, 103 men (44.2%) had a PSA doubling time that was negative (ie, half-life) or longer than 10 yr. Men detected at rescreening were significantly more likely to be on active surveillance, and they had more beneficial characteristics. Deferred treatment was elected in 82 cases (29.0%). Overall survival was 89% after 8 yr; the cause-specific survival was 100%. CONCLUSIONS: This report shows a beneficial, although preliminary, outcome of screen-detected men managed on active surveillance. Men were more likely to be on active surveillance if the disease was detected at repeated screening. The report also shows that an important proportion of men have prolonged PSA doubling times, although the value of this parameter has not been established in untreated men.

Prevalence, treatment modalities and prognosis of familial prostate cancer in a screened population.

PURPOSE: A family history of prostate cancer is an important risk factor for this disease. The clinical presentation and prognosis of familial disease remain uncertain. In this study these entities are evaluated in the first and second rounds of a screening program in The Netherlands. MATERIALS AND METHODS: Of all men randomized in the Rotterdam section of the ERSPC, 19,970 men were eligible for screening. Information regarding the family history was obtained by a self-administered questionnaire at baseline. RESULTS: In the prevalence screen the cancer detection rate in 1,364 men (7.1%) with a positive family history was 7.7% (106 cancers in 1,364 screened men with a positive family history) while the positive predictive value of the biopsies was 32.2% (154 cancers of 532 biopsies). In 12,803 sporadic cases the detection rate was 4.7% and the positive predictive value was 23.6% (p <0.0001 and 0.003, RR 1.63). No clinicopathological differences were found in the 1,559 men diagnosed in the first and second rounds. The overall biochemical-free survival rate after a mean followup of 56.8 months (range 0 to 129.9) was 76.8%, and was not significantly different in familial and sporadic cases (p = 0.840). These findings were consistent for the specific treatment modalities as well. CONCLUSIONS: Although screened men 55 to 75 years old with a father or a brother having prostate cancer themselves are at a substantially greater risk for the disease, the clinical presentation, treatment modalities and prognosis by biochemical progression are not different compared to sporadic cases.

Screening for prostate cancer without digital rectal examination and transrectal ultrasound: results after four years in the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam.

BACKGROUND: Omission of DRE/TRUS as biopsy indication results in fewer unnecessary biopsies, but may increase the risk of missing potentially aggressive prostate cancers (PCs). In 1997, the biopsy indication within the ERSPC was changed from a PSA cut-off of 4.0 ng/ml and/or abnormal DRE/TRUS (group-1) to solely a PSA cut-off of 3.0 ng/ml (group-2). We estimated the effect of omitting DRE/TRUS by comparing the results of a re-screening 4 years after initial screening to the original policy. METHODS: We compared rate and characteristics of detected PCs in the second round in men initially screened in group-1 (N=5,957) or group-2 (N=8,044). Additionally, we compared the rate of interval cancers (ICs) after screening with and without DRE/TRUS. RESULTS: There was no significant difference in second round cancer-detection-rates (group-1, 3.0%; group-2, 2.7%), positive-predictive-values (group-1, 23.9%; group-2, 26.3%), and number of poorly-differentiated tumors (group-1, 2.6%; group-2, 3.8%). Most PCs were clinically confined to the prostate. Eleven ICs were detected in each group (0.18 and 0.14%). CONCLUSIONS: Omitting DRE/TRUS did not result in an increased IC- or PC-detection. However, considering the natural history of PC, the 4-year follow-up may be too short to draw a definitive conclusion.

Additional use of [-2] precursor prostate-specific antigen and "benign" PSA at diagnosis in screen-detected prostate cancer.

OBJECTIVES: To evaluate the adjuvant clinical use of [-2] precursor prostate-specific antigen ([-2]pPSA), which is associated with prostate cancer (PCa), and "benign" PSA, related to benign prostatic hyperplasia, in selecting a treatment strategy in patients with screen-detected PCa. METHODS: Research-use immunoassays (Beckman Coulter) were used to measure [-2]pPSA, sum [-7, -5, -4, and -2]pPSA, and benign PSA from the frozen serum of participants from the screen arm of the European Randomized Study of Screening for Prostate Cancer, section Rotterdam, diagnosed with PCa with a serum PSA level lower than 15 ng/mL. We compared men with relatively benign PCa (Epstein's criteria; group 1) and men with arbitrarily defined aggressive PCa characteristics (Gleason score greater than 4 + 4 and more than four cores with PCa invasion or pT3C disease; group 2). RESULTS: The data of 61 patients were evaluated. The median age in both groups was 68 years. Total PSA performed best in a univariate analysis, although in the multivariate analysis, the combination of pPSA and percent free PSA could correctly predict 95.5% of group 1 and 82.4% of group 2. The pPSA and percent free PSA forms remained statistically significant in the multivariate analysis of a subgroup of 30 participants normalized for PSA level and prostate volume; combined they correctly identified 89.5% and 54.5% of patients identified as having relatively favorable and aggressive PCa characteristics, respectively. CONCLUSIONS: Adjuvant clinical use of pPSA over traditional parameters in selecting treatment strategies for men with PCa cannot yet be definitely determined. However, the promising results in a subgroup analysis warrant further investigation.

Prostate cancer characteristics and prostate specific antigen changes in screening detected patients initially treated with a watchful waiting policy.

PURPOSE: We evaluated prostate cancer (PCa) characteristics at diagnosis and changes in prostatic specific antigen (PSA) with time in males with screening detected PCa that was initially managed with a watchful waiting policy. MATERIALS AND METHODS: Patients with histologically proven PCa and PSA less than 10 ng/ml were selected from the European Randomized Study of Screening for Prostate Cancer, section Rotterdam. The choice of initiating a watchful waiting policy was patient desire or physician advice. PSA slope and PSA doubling time (PSADT) were calculated in patients with 3 or more PSA tests results available. RESULTS: A total of 191 patients were included. Mean age at diagnosis was 69 years and mean PSA was 3.9 ng/ml. Of the patients 92.6% had a Gleason score of 3 + 3 or lower, 133 had a followup of greater than 12 months (mean 40) and 35 (29.2%) had a negative PSA slope. Mean PSADT was 9.7 years (range 0.3 to 155) in 85 males with a positive PSA slope. During followup 30 patients changed therapy. CONCLUSIONS: Watchful waiting remains a controversial prostate cancer treatment strategy. In select screening detected patients with PCa there appears to be a subgroup with stable or even decreasing PSA values with time. These males could profit from a watchful waiting policy with possible deferred treatment. Together with conventional tumor parameters at diagnosis PSADT and PSA slope during followup could be used to monitor tumor activity and possibly aid in determining the time of deferred treatment. Further followup is mandatory to validate these results.

Prostate-specific antigen change in the European Randomized Study of Screening for Prostate Cancer, section Rotterdam.

OBJECTIVES: To determine the prostate-specific antigen (PSA) velocity, PSA slope, and PSA doubling time (PSADT) in men with positive biopsies, negative biopsies, and no biopsy indications 4 years after an initial screening; and to use this information to improve the test characteristics in the early detection of prostate cancer and provide normal values for these parameters in screened men with and without evidence of prostate cancer. METHODS: Within the European Randomized Study of Screening for Prostate Cancer, section Rotterdam, we identified 9575 men with a second determination of PSA 4 years after the initial screening. These men were divided into three groups: men with positive biopsies, negative biopsies, and no biopsy indications in the second round (PSA less than 3.0 ng/mL). The predictive values of PSA dynamics for detection of prostate cancer were calculated. RESULTS: The mean PSA velocity of men with prostate cancer was 0.62 ng/mL/yr versus 0.46 ng/mL/yr for men with a negative biopsy (P = 0.001). The mean PSADT for men with prostate cancer was 5.1 years and for those with a negative biopsy it was 6.1 years (P = 0.002). The PSADT for men with no indication for biopsy was 25.1 years. However, receiver operating characteristic analyses revealed only a moderate value for these test parameters in predicting biopsy outcome. CONCLUSIONS: The mean values of PSA velocity, PSA slope, and PSADT in a rescreened population differed significantly between men with and without prostate cancer. However, in predicting the biopsy outcome, the PSA dynamics were of limited value.

Development of renal function after neonatal urinary ascites due to obstructive uropathy.

PURPOSE: Neonatal urinary ascites is a rare complication of obstructive uropathy with possible lethal outcome if not treated adequately. We demonstrate that with adequate therapy the survival rate can be high and long-term survival, kidney function and lower urinary tract function of patients with urinary ascites can be good. MATERIALS AND METHODS: The study included 4 females and 8 males born with urinary ascites. Followup ranged from 3 to 14 years. Blood analysis for renal function, electrolytes and blood gas was performed at hospitalization and during followup. Ultrasound, cystourethrograms or cystoscopy showed the site of obstruction and leakage of urine. All patients were initially treated with drainage of the ascites and decompression of the obstructed urinary tract. All patients underwent surgery to remove the obstruction and reconstruct the urinary tract. Bladder and kidney function was evaluated at long-term followup. RESULTS: All patients had severe abdominal distention at presentation. Severe metabolic acidosis was present in cases that had not been detected prenatally or immediately after birth. Two patients died of causes related to pulmonary hypoplasia. Surprisingly urinary continence and renal function were good in 9 of 10 survivors. CONCLUSIONS: Long-term outcome of bladder and kidney function is surprisingly good in cases of severe obstructive uropathy with ascites. Intrauterine pressure relief of the bladder through urinary extravasation protects renal function and this decompression of the urinary tract prevents severe secondary changes to bladder function. Although not proven we believe that high intrauterine pressures in the abdominal cavity are prevented by peritoneal absorption of the extravasated urine and consequent dialysis through the placenta.